Omeprazole, chemically 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and its therapeutic uses were disclosed in European Patent No. 5129. Omeprazole is a well-known gastric acid secretion inhibitor, and is useful as an anti ulcer agent. Omeprazole has a stereogenic center at sulfur and therefore exist as two optical isomers such as R-omeprazole and S-omeprazole (esomeprazole).
The alkaline salts of (S)-enantiomer of omeprazole (esomeprazole), the pharmaceutical preparations of these salts and the method of treatment of gastric acid-related diseases using them were disclosed in U.S. Pat. Nos. 4,738,974, 5,877,192 and 5,714,504. The patents U.S. Pat. Nos. 4,738,974, 5,877,192 and 5,714,504 are incorporated herein by reference.
These compounds and structurally related compounds have a stereogenic center at sulfur and therefore exist as two optical isomers. The resolution processes of racemates of these compounds were for example disclosed in DE 4035455 and WO 94/27988. According to these processes chiral ether such as fenchyloxymethyl or chiral acyloxy methyl group such as mandeloyl—is introduced into the 1-position of benzimidazole ring of racemic sulfoxide compound to obtain a diastereomeric mixture, diastereomers are then separated and desired isomer is liberated from a separated diastereomer. The process requires either the preparation of fenchyloxymethyl chloride and then reaction with the racemic compound; or introduction of chloromethyl group on 1-position of benzimidazole ring, followed by reaction with the chiral auxiliary. We find that these intermediates are difficult to prepare and involve in many steps.
WO97/02261 disclosed a process for the optical purification of certain enantiomerically enriched benzimidazole derivatives by using a crystallization method.
Chinese Patent No. 1087739 disclosed a method of preparing esomeprazole by using (S)-(−)-binol (β-binapthol) as an optical resolution agent by inclusion of complex with (S)-(−)-binol
Chinese Patent No. 1223262 was related to a process for the preparation of certain optically pure benzimidazole derivatives by inclusion complexation with binaphthyl phenol derivative.
The resolution of sulfoxide compounds including racemic omeprazole were described in WO 2004/002982. The method requires expensive reagents like titanium compounds, two chiral reagents namely diethyl-D-tartarate and L-Mandelic acid.
Enantioselective synthesis was described for example in Euro. J. Biochem. 166 (1987) 453 and U.S. Pat. No. 5,948,789. Disadvantages of these methods are that strict control of conditions is to be maintained and strict control of quantities of oxidizing agents is required for avoiding oxidation of desired sulfoxide to sulfone impurity. Moreover, these methods require expensive reagents like titanium isoproxide and diethyl-D-tartarate.
The process for the preparation of racemic benzimidazole sulfoxides such as omeprazole, useful as starting materials for preparing enantiomerically pure benzimidazole sulfoxides, from their corresponding sulfides involves a problem of over oxidation to form sulfone impurities.
WO2005/105786 and WO2005/116011 described the resolution methods for racemic benzimidazole sulfoxides.
WO2006/094904 disclosed a process for the resolution of 2-(2-pyridimylmethylsulfinyl)-benzimidazole derivatives by the inclusion complex with [1,1′-binapthalene]-2-2′-diol in presence of amine.
WO2007/013743 disclosed an improved optical resolution process for preparing optically pure esomeprazole and its salts by inclusion complex with (S)-(−)-binol.
WO2007/074099 disclosed process for the preparation of optically pure benzimidazole derivatives by inclusion complex with (S)-1,1,2-triphenyl-1,2-ethanediol.
WO2008/092939 disclosed a process for the preparation of substantially optically pure omeprazole with the formation of a complex by using chiral amine or chiral quaternary ammonium salt.
We have discovered a novel process for optical purification of esomeprazole. The object of the present invention is to provide an improved and commercially viable process for optical purification of esomeprazole or its salts.